Sealed assembly for separation of blood with anti-red cell barrier

ABSTRACT

A self-contained fluid separator assembly capable of separating blood into its component parts of plasma or serum, the light phase, and cellular portion, the heavy phase, is disclosed. The assembly comprises a container having a first open end for receiving blood for subsequent separation, a second open end for removing the separated plasma or serum and a closure sealing each open end of the container, the closures being formed of a self sealing elastomeric material which is penetrable by a cannula. A piston is slidably disposed in the container having its lateral outer surfaces in sealing contact with the inner surfaces of the container. Pressure responsive valve means is provided on the piston which is normally closed when there is a minimum pressure differential on each side of the piston and which automatically opens in response to a substantial pressure differential so that when the container is subjected to centrifugal force the blood separates into its light phase and heavy phase and the valve means automatically opens as the piston moves down through the light phase while retaining sealing engagement with the inner surfaces of the container. A frangible seal means is also provided to seal said piston in a position opposite to the end for receiving blood with means for removing said frangible seal means. The seal insures that the piston is not contaminated with red blood cells prior to separation of the blood specimen. Stop means is formed on the container so that the piston as it moves through the light phase will contact the stop means and stop a predetermined distance from the bottom closure means, the pressure differential is terminated and the valve means automatically shifts from the open position to the closed position to provide an impervious barrier between the separated phases of the blood.

United States Patent [1 1 [111 3,882,021 Ayres [451 May 6, 1975 1 SEALEDASSEMBLY FOR SEPARATION OF serum, the light phase, and cellular portion,the heavy BLOOD WITH ANTI-RED CELL BARRIER [52] US. Cl. 210/136;210/359; 210/516;

210/D1G. 23 [51] Int. Cl. 801d 33/00 [58] Field of Search 23/230 B,258.5, 259, 292;

128/2 F, 214 R, 218 M, 272; 210/83, 84, 109, 131, 359, 514-518, DIG. 23,DIG. 24, 97, 136; 233/1 A, 1 R, 26

[56] References Cited UNITED STATES PATENTS 2,305,278 12/1942 Smith128/218 M 3,508,653 4/1970 Coleman 210/DIG. 23 3,537,605 11/1970 Solowey128/218 M X 3,586,064 6/1971 Brown et al. 233/26 3,786,985 1/1974Blaivas 233/26 Primary Examiner-Samih N. Zahama AssistantExaminer-Robert H. Spitzer Attorney, Agent, or Firml(ane, Dalsimer,Kane, Sullivan and Kurucz 5 7] ABSTRACT A self-contained fluid separatorassembly capable of separating blood into its component parts of plasmaor phase, is disclosed. The assembly comprises a container having afirst open end for receiving blood for subsequent separation, a secondopen end for removing the separated plasma or serum and a closuresealing each open end of the container, the closures being formed of aself sealing elastomeric material which is penetrable by a cannula. Apiston is slidably disposed in the container having its lateral outersurfaces in sealing contact with the inner surfaces of the container.Pressure responsive valve means is provided on the piston which isnormally closed when there is a minimum pressure differential on eachside of the piston and which automatically opens in response to asubstantial pressure differential so that when the container issubjected to centrifugal force the blood separates into its light phaseand heavy phase and the valve means automatically opens as the pistonmoves down through the light phase while retaining sealing engagementwith the inner surfaces of the container. A frangible seal means is alsoprovided to seal said piston in a position opposite to the end forreceiving blood with means for removing said frangible seal means. Theseal insures that the piston is not contaminated with red blood cellsprior to separation of the blood specimen. Stop means is formed on thecontainer so that the piston as it moves through the light phase willcontact the stop means and stop a predetermined distance from the bottomclosure means, the pressure differential is terminated and the valvemeans automatically shifts from the open position to the closed positionto provide an impervious barrier between the separated phases of theblood.

6 Claims, 2 Drawing Figures SEALED ASSEMBLY FOR SEPARATION OF BLOOD WITHANTI-RED CELL BARRIER BACKGROUND OF THE INVENTION 1. Field of theInvention The invention concerns apparatus for the separation andisolation of blood plasma and blood serum from blood mixtures.

2. Brief Description of the Prior Art It is known to separate blood intoits component parts by centrifugation, particularly employing a sealedcontainer such as is disclosed in US. Pat. No. 2,460,641. This patentdiscloses a container having a closure at its open end which is capableof being penetrated by a cannula through which blood passes into thecontainer. Clinical laboratories have heretofore used this device tocollect a blood sample for subsequent separation into a light phase,i.e. the serum or plasma and the heavy phase, i.e. the cellular portion.The light phase is then decanted from the cellular portion by anyconventional means, for example by the use of a syringe fitted with acannula, or a pipette, or the like.

As apparatus also heretofore employed for the separation of blood isdisclosed in U.S. Pat. No. 3,508,653. This patent discloses aself-contained assembly for separation of body fluid such as blood inwhich a deformable piston is disposed in the container and is positionedinitially adjacent the stopper for closing the container. After theblood to be separated is in the container the assembly is centrifuged.After the blood is separated, incresed centrifugal force is applied tothe container, the seal between the inner surface of the container andpiston is broken and the piston is deformed, moving down through thelight phase with the light phase passing solely around the lateralsurfaces of the piston and the inner surfaces of the container. When thepiston reaches the interface between the light phase and the heavyphase, the piston movement is re-established between the inner surfaceof the container and the resilient piston to present a barrier betweenthe two phases.

Disclosed in my U.S. Pat. No. 3,779,383 is a serum plasma separatoremploying a piston to effect a sealed isolation of separated bloodphases. The present invention is an improvement over that device. Thepiston component of the earlier disclosed invention is subject tocontact with blood as it is received into the container member. Onoccasion, red blood cells may adhere to the piston member duringseparation of the blood phases. The light phase blood component passesby the piston during piston descent by centrifugation, and mayoccasionally dislodge a few red blood cells, carrying them up and mixingthem with the light phase component.

The present invention obviates the possibility of red blood cells comingin contact with the piston member during filling of the separatorassembly and thereby reduces the likelihood that the desired bloodplasma or serum will be contaminated with any red blood cells.

Furthermore, those separator devices of the prior art having filterelements associated with the piston are subject to clogging by red bloodcells during filling of the separator assembly with blood. This problemis also obviated by the present invention which has a means ofpreventing the red blood cells from contacting the piston or associatedparts thereof.

Other devices known to the art are generally the filtration deviceswhich separate blood into its component phases such as those disclosedin US. Pat. Nos. 3,481,477 and 3,512,940.

SUMMARY OF THE INVENTION The invention comprises: a self-contained fluidseparator assembly capable of separating blood into its component partsof plasma and serum and cellular part comprising (a) a container havinga first open end which is adapted to receive blood for subsequentseparation into a light phase and a heavy phase and a second open endfor removing the separated light phase; (b) closures sealing the openends of the container, the closures being formed of a self-sealingelastomeric material which is penetrable by a cannula; (c) a pistonhaving a specific gravity relatively greater than the cellular portionof the blood and slidably mounted in the container and having means oran outer surface in sealing engagement with an inner surface of thecontainer; (d) pressure responsive valve means associated with saidpiston, said valve means being normally closed when there is a minimumof pressure differential on different portions of the valve means andwhich automatically opens in response to a substantial pressuredifferential so that when said container is subjected to moderatecentrifugal force the blood separates into its light phase and heavyphase but the piston stays in the upper portion of the container andsubsequently when increased centrifugal force is used the valve meansautomatically opens with the light phase passing up through the valvemeans enabling the piston to move down through the light phase whileretaining sealing engagement with the inner surfaces of the container;(e) frangible seal means sealing said piston in a position opposite tothe first end for receiving blood; (f) means for removing said frangibleseal; and (g) mechanical stop means on the container whereby the pistonwhen moving through the light phase will stop a predetermined distancefrom one of the ends of the container followed by termination of thedifferential pressure which permits the valve means to automaticallyshift from an open position to a closed position to provide animpervious barrier between the separated light phase and heavy phase ofthe blood.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a cross-sectional sideelevational view of a separator assembly of the invention illustrating acannula penetrating one of the closures through which blood isintroduced into the container prior to separation.

FIG. 2 is a view similar to FIG. 1 illustrating the separtion of theblood into the light phase and heavy phase with the piston engaging thestop means.

DETAILED DESCRIPTION OF THE INVENTION For a better unerstanding of theinvention, a description of the drawings of the illustrative embodimentsis had, particularly with respect to the embodiments shown in FIGS. 1and 2.

Referring to FIG. 1, it is seen that the separator assembly 10 comprisesa tubular member or container 12 having mounted in open ends 11 and 15,closures l4 and 16. Closures 14 and 16 are made of a self-sealingelastomeric material such as rubber which are capable of receivingcannula 18 penetrated therethrough as illustrated in FIG. 1, forconducting blood 5 into the container. When the cannula is removed theclosure is resealed with no loss of blood 5 passing through thepenetration portion as illustrated in FIG. 2.

Closure 14 is formed having a depending cylindrical body portion and aflanged head portion 22 integrally formed therewith. Body portion 20 hasa diameter slightly greater than the internal diameter of the container12 so that closure 14 when mounted into end 11 provides a pressure fitto seal the end. Head portion 22 is preferably shaped in the form of ahexagon and is slightly greater in diameter than body portion 20 whichpermits the assembly to be positioned on its side without danger ofrolling. An axial recess 24 is provided for easy access through stopper16 which reduces the force required to penetrate with cannula 18.

Stopper 16 is formed preferably of the same material as stopper 14 buthas different configuration and dimensions. Stopper 16 has a cylindricalbody portion 28 and in integrally formed head portion 30 having an axialrecess 24. Body portion 28 has an annular recess 29 to provide aself-sealing penetrable zone 31 to facilitate insertion of cannula 18with minimum force while maintaining a sealed closure. As noted above,stopper or closure 14 as well as 16 is inserted into ends 11 and 15 incompression to maintain ends 11 and 15 of container 12 in sealedengagment.

Tubular member or container 12 is formed preferably of glass but asuitable plastic material may be employed. Intermediate ends 11 and 15of tubular member 12 is an annular groove 32 which forms a stop means 34as a part of the inner surfaces 13 of container 12. Thus, as pistonmoves from the initial starting position illustrated in FIG. 1 to theterminal position after the separation of the light phase 5a from theheavy phase 515 as shown in FIG. 2 the piston comes to rest at the stopmeans 34 formed by annular groove 32 of container 12.

Piston 40 includes a tubular metal insert 52 which is mounted in annularrecess 54 of piston 40. Metal insert 52 is preferably made of stainlesssteel or other rigid, chemically inert material having a specificgravity substantially greater than blood. Piston 40 is formed ofelastomeric material and is provided with annnular recess 54 which isdimensioned to receive tubular member 52 in an interference fit so thatno air space remains in annular recess 54.

The elastomeric portion of piston 40 comprises an outer wall 48 andspaced therefrom is inner wall 46 which defines annular recess 54.Formed integrally with wall 48 are a plurality of axially spaced sealingrings 50 which contact the inner wall surface 13 of container 12 insealing engagement. piston 40 when mounted in container 12 will maintainsealing contact with inner wall 13 of container 12 throughout its pathof travel within container 12 as hereinafter described. During acentrifuging operation piston 40 is subjected to centrifugal forceswhich starts to move the piston downwardly which creates a pressuredifferential on the opposite sides of the top wall portion 44 of piston40. Top wall portion or diaphragm 44 has a relatively small thicknessand lies adjacent stopper 14 in its initial position as seen in FIGv l.Diaphragm 44 is made of a resilient material and is provided with atleast one aperture 42 extending therethrough. Wall portions 46 and 44 ofpiston 40 define an axial annular recess or throat 80 within piston 40which leads from the lower surface 82 of piston 40 to apertures 42. Asthe assembly is being subjected to centrifugal forces the light phasewhich is separated from the blood will pass into throat and be guided toapertures 42. Also, since the centrifugal forces acting on piston 40will cause it to slide downwardly and thereby generate a hydrostaticforce greater than the force of the light phase being exerted againstthe top of diaphragm 44 apertures 42 will automatically open and willpermit light phase liquid to flow upwardly and thereby enable piston 40to move from its initial position of FIG. 1 to its final position ofFIG. 2 while maintaining sealing engagement with the inner wall 13 ofcontainer 12. When piston 40 stops its movement in container 12 andcomes to rest on stop means 34, the pressure differential on each sideof diaphragm 44 is substantially equalized and valve means 42automatically shifts from the open position to the closed position eventhough the assembly is being subjected to centrifugal forces.

As shown in FIG. 1, a filter 60 substantially fills the throat 80.Filter 60 is an optional element employed when it is desired to filterthe blood plasma or serum prior to its passage through valve apertures42. Also as shown in FIG. 1, piston 40 with all of its component andassociate structures is isolated from lower portion 85 of container 12by a frangible seal 88. This seal 88 forms a protective barrier,preventing blood 5 from contacting piston 40 during the assembly bloodfilling operation. Seal 88 may be any frangible sealant material whichis nonreactive with blood. The seal 88 material should also have aspecific gravity exceeding the specific gravity of the heavy phase ofblood. Illustrative of seal 88 materials are polymeric waxes such aspolyethylene polymer waxes of high molecular weight, parrafin, beeswaxand the like. Higher specific gravity sealants can be prepared by mixingthe above seal materials with dense inert fillers such as glass beads,clays, metallic powders and like filler materials.

Illustrated in FIG. 1 is a seal breaking disc which may be fabricated ofany dense material which is nonreactive with blood such as stainlesssteel or a dense ceramic. The density of disc 90 is such that it has aspecific gravity exceeding the specific gravity of the heavy phaseblood. Disc 90 is conveniently nested in the lower portion of piston 40and preferably is held in place by a light interference fit with wall 89formed by a recess in the lower surface 82 of piston 40.

As illustrated in FIG. 2, piston 40 has completed its travel withincontainer 12 and is stopped from further movement in container 12 bystop means 34 and valve means 42 is closed.

When operating the separator assembly of the invention herein it ispreferred that the assembly be evaculated of air so that when cannula 18penetrates closure 16 blood will automatically fill container 12.

After cannula 18 is withdrawn and container 12 is filled with blood theassembly of the invention is placed in a centrifuge and the blood isseparated employing relatively low centrifugal forces which do notactivate the seal breaking means or cause the piston 40 to move from itsinitial position. Thereafter the rotational speed of the centrifuge isincreased, whereby the disc 90 breaks loose and falls to the lower end15 of container 12, breaking seal 88 in its passage. The broken sealfragments 92 also descent to the lower end 15 of container 12 due totheir density and only moderate adhesiveness. The higher centrifugalforces also cause the piston to slide and a substantial differentialhydrostatic pressure develops on the piston diaphragm 44, the valvemeans 42 automatically opens and the piston 40 moves downwardly throughthe light phase 5a with the light phase passing through the throat 80,through the filter 60 and valve means 42. Piston 40 maintains sealingengagement with the inner wall 13 of container 12 during descent to stop34. The piston 40 completes its movement when it engages stop means 34,this terminates the pressure differential on piston diaphragm 44,automatically closing the valve means 42 while the assembly is stillsubjected to centrifugal forces. Diaphragm 44 then presents animpervious barrier between the light 5a and heavy 5b phases of the blood5 when piston 40 is in the position illustrated in FIG. 2. Centrifugalforces are then terminated and the separated blood sample is ready foruse in a diagnostic procedure.

What is claimed is:

l. A self-contained fluid separator assembly capable of separating bloodinto its component phases of light phase plasma or serum and heavy phasecellular portion comprising:

a. a container having a first open end which is adapted to receive bloodfor subsequent separation into a light phase and a heavy phase and asecond open end for removing the separated light phase;

b. closures sealing the open ends of the container, the closures beingformed of a self-sealing elastomeric material which is penetrable by acannula;

c. a piston having a specific gravity relatively greater than the heavyphase portion of the blood and slidably mounted in the container andhaving means on an outer surface in sealing engagement with an innersurface of the container;

d. pressure responsive valve means associated with said piston, saidvalve means being normally closed when there is a minimum of pressuredifierential on different portions of the valve means and whichautomatically opens in response to a substantial pressure differentialso that when said container is subjected to moderate centrifugal forcethe blood separates into its light phase and heavy phase but the pistonstays in the upper portion of the container, and subsequently whenincreased centrifugal force is used the valve means automatically openswith the lighht phase passing up through the valve means enabling thepiston to move down through the light phase while retaining sealingengagement with the inner surfaces of the container;

. frangible seal means in a position opposite to the first end forreceiving blood and between said first end and said piston to isolatesaid piston from contact with the blood;

f. means for breaking said frangible seal, said seal and said means forbreaking said seal being constructed and arranged so that when thecentrifugal force reaches a predetermined value, the seal is broken bysaid seal breaking means; and

g. mechanical stop means on the container whereby the piston when movingthrough the light phase will stop a predetermined distance from one ofthe ends of the container followed by termination of the differentpressure with permits the valve means to automatically shift from anopen position to a closed position to provide an impervious barrierbetween the separated light phase and heavy phase of the blood.

2. The self-contained fluid separtor of claim 1 wherein said containercomprises a tubular body open at each end in which closures formed ofelastomeric material are mounted in sealing engagement with the tubularbody and a piston is disposed adjacent one of said closures.

3. The self-contained fluid separator of claim 1 wherein the pistonincludes a rigid tubular sleeve mounted in a generally tubular outerbody portion formed of rubber and having a plurality of spaced axialribs on its outer portion for sealing engagement with the inner walls ofthe container and a diaphragm forming a wall across one end of thegenerally tubular rubber sleeve and having at least one aperture formedtherein which is normally closed but which automatically opens whensubjected to a substantial pressure differential on opposite sides ofthe diaphragm.

4. The self-contained fluid separator of claim 1 wherein the piston hasa tubular metal sleeve mounted in sealing engagement in a complementaryannular recess formed in a rubber body portion of said piston, having aninterference fit so that substantially no air space is provided betweenthe walls defining the annular recess and the inner and outer walls ofthe rigid tubular member.

5. The self-contained fluid separator of claim 1 wherein the stop meansformed on the container is an annular groove interposed between the endsof the container forming an annular rim on the inner surface of thecontainer so that said piston is prevented from passing the stop meanswhen subjected to centrifugal forces.

6. The self-contained fluid separator of claim 1 wherein the pistonincludes a filter component located in the path of said light phasepassing up through the valve means.

1. A self-contained fluid separator assembly capable of separating bloodinto its component phases of light phase plasma or serum and heavy phasecellular portion comprising: a. a container having a first open endwhich is adapted to receive blood for subsequent separation into a lightphase and a heavy phase and a second open end for removing the separatedlight phase; b. closures sealing the open ends of the container, theclosures being formed of a self-sealing elastomeric material which ispenetrable by a cannula; c. a piston having a specific gravityrelatively greater than the heavy phase portion of the blood andslidably mounted in the container and having means on an outer surfacein sealing engagement with an inner surface of the container; d.pressure responsive valve means associated with said piston, said valvemeans being normally closed when there is a minimum of pressuredifferential on different portions of the valve means and whichautomatically opens in response to a substantial pressure differentialso that when said container is subjected to moderate centrifugal forcethe blood separates into its light phase and heavy phase but the pistonstays in the upper portion of the container, and subsequently whenincreased centrifugal force is used the valve means automatically openswith the lighht phase passing up through the valve means enabling thepiston to move down through the light phase while retaining sealingengagement with the inner surfaces of the container; e. frangible sealmeans in a position opposite to the first end for receiving blood andbetween said first end and said piston to isolate said piston fromcontact with the blood; f. means for breaking said frangible seal, saidseal and said means for breaking said seal being constructed andarranged so that when the centrifugal force reaches a predeterminedvalue, the seal is broken by said seal breaking means; and g. mechanicalstop means on the container whereby the piston when moving through thelight phase will stop a predetermined distance from one of the ends ofthe container followed by termination of the different pressure withpermits the valve means to automatically shift from an open position toa closed position to provide an impervious barrier between the separatedlight phase and heavy phase of the blood.
 2. The self-contained fluidsepartor of claim 1 wherein said container comprises a tubular body openat each end in which closures formed of elastomeric material are mountedin sealing engagement with the tubular body and a piston is disposedadjacent one of said closures.
 3. The self-contained fluid separator ofclaim 1 wherein the piston includes a rigid tubular sleeve mounted in agenerally tubular outer body portion formed of rubbeR and having aplurality of spaced axial ribs on its outer portion for sealingengagement with the inner walls of the container and a diaphragm forminga wall across one end of the generally tubular rubber sleeve and havingat least one aperture formed therein which is normally closed but whichautomatically opens when subjected to a substantial pressuredifferential on opposite sides of the diaphragm.
 4. The self-containedfluid separator of claim 1 wherein the piston has a tubular metal sleevemounted in sealing engagement in a complementary annular recess formedin a rubber body portion of said piston, having an interference fit sothat substantially no air space is provided between the walls definingthe annular recess and the inner and outer walls of the rigid tubularmember.
 5. The self-contained fluid separator of claim 1 wherein thestop means formed on the container is an annular groove interposedbetween the ends of the container forming an annular rim on the innersurface of the container so that said piston is prevented from passingthe stop means when subjected to centrifugal forces.
 6. Theself-contained fluid separator of claim 1 wherein the piston includes afilter component located in the path of said light phase passing upthrough the valve means.